Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiviral drug used in the treatment of acquired immunodeficiency syndrome, zidovudine, has proved effective in ameliorating the morbidity and mortality associated with human immunodeficiency virus infection. However, associated with zidovudine is the development of severe bone marrow toxicity manifested by anemia, neutropenia, and occasionally thrombocytopenia. We report the results of studies that demonstrate the ability of basic fibroblast growth factor (B-FGF) to reduce zidovudine toxicity to several classes of hematopoietic progenitors (granulocyte-macrophage, CFU-GM; megakaryocyte. CFU-Meg; and erythroid, BFU-E) from normal murine, human, and murine retrovirus-infected bone marrow cells when cocultured with zidovudine in vitro. Optimal response to B-FGF was observed at a dose concentration of 10 ng/ml. The specificity of B-FGF was demonstrated in the presence of protamine sulfate, an effective inhibitor of B-FGF mitogenic activity. In addition, synergistic activity of B-FGF on zidovudine-induced hematopoietic stem cell toxicity was observed in the presence of interleukin 1 (IL-1) (30 ng/ml). These studies demonstrate that B-FGF is capable of reducing the hematopoietic toxicity associated with zidovudine and that such an effect can be amplified in the presence of IL-1.
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PMID:In vitro modulation of the toxicity associated with the use of zidovudine on normal murine, human, and murine retrovirus-infected hematopoietic progenitor stem cells with basic fibroblast growth factor and synergistic activity with interleukin-1. 131 78

Anaemia in rheumatoid arthritis (RA) is a common and debilitating complication. The most common causes of this anaemia are iron deficiency and anaemia of chronic disease. Investigations have suggested that interleukin 1 (IL-1) or tumour necrosis factor (TNF), or both, from monocytes associated with chronic inflammation are responsible for the anaemia of chronic disease. On bone marrow examination anaemia of chronic disease is characterised by the diversion of iron from the erythropoietic compartment into marrow macrophages. This phenomenon is termed failure of iron utilisation. In this study, CFU-E (colony forming unit erythroid; late red cell precursors) and BFU-E (burst forming unit erythroid; early red cell precursors) stem cells were cultured from 10 normal marrow samples and 12 marrow samples from patients with RA with iron deficiency anaemia and 10 samples from patients with RA with failure of iron utilisation. All patients with RA were anaemic (haemoglobin less than 100 g/l), Potential accessory or inhibitory cells of erythropoiesis (CD4, CD8, or CD14 positive cells) were removed before culture. Control marrow samples were studied in a similar manner. Normal marrow samples yielded 377 (17) CFU-E and 133 (6) BFU-E (mean (SD)) colonies for each 2 x 10(5) light density cells plated. CD4 ablation caused reductions of 62 and 100% in CFU-E and BFU-E colonies respectively. CD14 removal resulted in considerable but lesser reductions of 46% for CFU-E and 25% for BFU-E. In both groups of patients with RA, CFU-E colony numbers were significantly lower than those seen in normal control subjects, 293 (17) for patients with iron deficiency anaemia and 242 (35) for patients with failure of iron utilisation. BFU-E colony numbers were 102 (13) and 108 (20) respectively. In patients with RA, CD4 removal caused a significantly greater loss of CFU-E colonies compared with normal control subjects. Cytolysis of CD14 positive cells caused a reduction in CFU-E colonies in the two RA groups which was similar to that seen in normal subjects. In conclusion, patients with RA seem to have fewer CFU-E progenitors but essentially normal numbers of BFU-E stem cells. Our data suggest a stimulatory role for marrow CD4 and CD14 cells in erythropoiesis in patients with RA. Monocytes-macrophages (CD14 positive) are known to be producers of IL-1 or TNF, or both, however, the predicted increase in the CFU-E colonies on removal of CD14 cells is not seen. Therefore, if IL-1 or TNF, or both, are responsible for the impairment of erythropoiesis in patients with RA, marrow macrophages are unlikely to be the source. Moreover, these results indicate the probability of erythropoietin resistance on the basis of diminished CFU-E colony formation in patients with RA.
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PMID:Anaemia of chronic disease in rheumatoid arthritis: effect of the blunted response to erythropoietin and of interleukin 1 production by marrow macrophages. 161 58

This report was aimed at confirming the potential clinical use for a genetically engineered glycosylated human interleukin-6 (rhIL-6) in hematopoiesis. Its tolerance and efficacy were assessed on hematopoietic restoration after neutron radiation-induced bone marrow injury on baboons, which represent an adequate model of parallelism for studying hematology in the human. The particular neutron radiation absorption pattern in the body allows the preservation of underexposed bone marrow areas that mimics an autotransplantation-like situation. An initial dose finding study (1 microgram up to 20 micrograms/kg/d for 8 consecutive days) in normal baboons established a dose-dependent response regarding the peripheral platelet count (range of increase, 1.5- to 4-fold). A significant elevation in white blood cell (WBC) count, as well as a substantial reversible normochromic normocytic anemia, were observed for the highest doses only (10 and 20 micrograms/kg/d). All rhIL-6 administered doses were clinically well tolerated. In myelosuppressed baboons, a selected dose of 10 micrograms/kg/d of rhIL-6 for 13 consecutive days significantly lessened the degree of induced thrombocytopenia as compared with the control group (P = .01) and shortened the time to occurrence of the nadir, showing that the onset of recovery occurs much earlier, ie, an average of 5 days (P = .003), in the treated group. Moreover, this accelerated platelet recovery is evidenced by an 8-day shorter mean time back to baseline values (P = .03) in the rhIL-6--treated animals. At this dose no effect was observed on the WBC recovery pattern. Importantly rhIL-6 did not accentuate the radiation-induced anemia and was clinically well tolerated. All tested monkeys recovered from their induced pancytopenia and no animal loss was recorded. IL-6, tumor necrosis factor, and IL-1 blood measurements are reported. In conclusion, rhIL-6 is a potent thrombopoietic factor for the treatment of induced thrombocytopenia in nonhuman primates at a clinically well-tolerated dose.
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PMID:Recombinant glycosylated human interleukin-6 accelerates peripheral blood platelet count recovery in radiation-induced bone marrow depression in baboons. 163 22

Deterioration in nutritional status occurs late in the progress of cancers at certain sites, but at all stages in patients with gastrointestinal cancer. Weight loss with decrease in body fat and muscle wastage, occurs to a varying degree. Superficially, the clinical condition resembles simple food deprivation. However, the derangements in metabolism are often and some patients show an elevated resting energy expenditure, disturbances of carbohydrate, fat and protein metabolism and generally, a failure to adapt to reduced food intake, which is characteristic of cachexia. Cancer cachexia then becomes characterized by signs of marked negative energy and protein balance, including hypoalbuminemia, weight loss, and anemia. On the other hand, toxohormone extracted from tumor tissues was considered as the main cause to produce cancer cachexia. However, it has become clearer that cytokines, e.g. cachectin/TNF, IL-1, LT and IFN gamma play an important role to produce cachexia. Patients who are malnourished have an incidence of postoperative complications double that seen in adequately nourished patients. The effectiveness of cancer-chemotherapy is also different in nutritional status of patients. Although in patients requiring hyperalimentation, enteral nutritional support may feasible and enteral feeding has a distinct metabolic advantage compared with parenteral feeding, there is a definite role for total parenteral nutrition in patients who have severe chronic radiation enteritis, side effect of chemotherapy, weight loss and malabsorption. Tentative weight gain and correction of hypoalbuminemia without improving patient survival may be expected by this intravenous hyperalimentation.
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PMID:[Palliative therapy in cancer 2. Nutrition control]. 169 91

Since interleukin 1 (IL-1) and erythropoietin (Epo) are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) anaemia we measured IL-1 alpha and Epo concentrations in 10 RA patients with chronic disease anaemia (CDA) and in 14 RA patients without anaemia. Anaemic RA patients had significantly higher IL-1 alpha concentrations than patients without anaemia. IL-1 alpha correlated negatively with haemoglobin and correlated positively with ESR. The results of a multivariate analysis showed that the best predictors of the presence and absence of anaemia were IL-1 alpha and ESR. No clinical parameters permitted a distinction between these two groups of patients. Epo levels were not different in anaemic and non-anaemic RA patients. No correlation was found between Hb and Epo, indicating the presence of an impaired Epo response in RA patients with CDA. We completed our study with the determination of the mean red cell lifespan and with the quantification of IgG and IgM bound to the surfaces of red blood cells (RBC-IgG and RBC-IgM) using a sensitive ELISA method. We observed a modest reduction in red cell survival in anaemic RA patients compared to normal controls. We did not find any correlation between Hb and red cell lifespan and between Hb and RBC-IgG. RBC-IgG and RBC-IgM were not found to be more elevated in anaemic RA than in non-anaemic patients.
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PMID:The role of interleukin 1, erythropoietin and red cell bound immunoglobulins in the anaemia of rheumatoid arthritis. 187 83

The etiology of the anemia of chronic disorders is complex. Factors which clearly contribute to the suppression of erythropoiesis are (a) reduced iron availability and (b) stimulation of the synthesis of immunomodulatory peptides such as IL-1, TNF-alpha and IFN-gamma, which inhibit the proliferation of erythrocytic progenitors in the bone marrow. The question as to whether lack of EPO is of general importance in the pathogenesis of the anemia of chronic inflammatory and malignant diseases is still a subject of controversy. The present in vitro studies show that IL-1 and TNF-alpha, but not IFN-gamma significantly lower the pO2-dependent formation of EPO in HepG2 cultures. In addition, clinical examples are given of anomalously low or high EPO levels in association with diseases involving the immune system. It is proposed that monokines and related immunomodulatory peptides could play a role in the control of the production of EPO.
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PMID:Modulation of the production of erythropoietin by cytokines: in vitro studies and their clinical implications. 212 66

Cachectin/tumor necrosis factor (TNF-alpha) is a macrophage-secreted cytokine initially found to be a lipoprotein lipase-suppressing serum factor in cachectic, parasite-infected animals. Cloning of the cDNA encoding the gene for cachectin enabled biosynthesis of recombinant human cachectin and proof that the protein is identical to TNF-alpha. Numerous biological activities have subsequently been attributed to this pluripotent cytokine. In addition to suppressing LPL, cachectin/TNF mediates decreased lipogenic enzyme synthesis in adipocytes, causing a state of "cellular cachexia" in vitro. Similarly, catabolic cellular energy responses are induced by cachectin/TNF in cultured skeletal muscle cells which exhibit accelerated glycogenolysis, enhanced lactate production, and increased expression of hexose transporters. Persistent cachectin/TNF production occurs in chronic infection and malignancy, and chronic exposure induces a cachexia syndrome characterized by anorexia, weight loss, and anemia. Acute systemic appearance of cachectin/TNF is capable of inducing a state of lethal shock, disseminated hemorrhagic necrosis, catabolic hormone release, and multiple organ injury. Inhibiting the toxic effects of cachectin/TNF with monoclonal anti-cachectin antibodies during overwhelming Gram-negative bacteremia confers protection against septic shock. In these studies, the unprotected controls succumbed within hours, but baboons immunized against cachectin/TNF did not develop the characteristic increases of IL-1, IL-6, or catabolic stress hormones and did not die, suggesting that cachectin/TNF is a pivotal, proximal factor in the humoral cascade mediating septic shock syndrome. Recent evidence indicates that when produced in lesser quantities, cachectin/TNF may participate in the degradative and reparative mechanisms of physiological tissue remodelling and homeostasis. Future studies of the immunological and metabolic effects of cachectin/TNF should lead to a better understanding of the pathogenesis of infection and inflammation.
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PMID:Metabolic responses to cachectin/TNF. A brief review. 219 78

The family of colony stimulating factors and interleukins influence all aspects of hematopoietic cell proliferation and differentiation. In most instances these hematopoietic growth factors have overlapping, pleiotropic effects and frequently regulate early progenitor cell proliferation and mature cell function. Currently, seven of these factors are in clinical trial: erythropoietin for treatment of anephric anemia, IL-2 in conjunction with LAC therapy, and IL-1, IL-3, G-CSF, GM-CSF, and M-CSF for stimulation of myelopoiesis and granulocyte-macrophage function after chemotherapy, irradiation, or bone marrow transplantation in patients with cancer. G-CSF and GM-CSF have also proved effective in treatment of congenital and idiopathic neutropenias and have had some efficacy in treatment of myeloid leukemias, myelodysplastic disorders, aplastic anemia, and acquired immunodeficiency syndrome (AIDS).
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PMID:Hematopoietic growth factors in cancer. 240 5

Fever is a prominent sign of an acute-phase response induced by microbial invasion, tissue injury, immunologic reactions, or inflammatory processes. This generalized host response is produced by a multiplicity of localized or systemic diseases and characterized by acute, subacute, or chronic changes in metabolic, endocrinologic, neurologic, and immunologic functions. The fundamental event is an initiation of the acute-phase response by the production of a mediated molecule called IL-1. This polypeptide is produced primarily from phagocytic cells such as blood monocytes, phagocytic lining cells of the liver and spleen, and other tissue macrophages. IL-1 produces a local reaction but also enters the circulation, acting as a hormone to mediate distant organ system responses to infection, immunologic reaction, and inflammatory processes. Fever is the result when IL-1 initiates the synthesis of prostaglandins, notably prostaglandin E2 in the thermoregulatory center located in the anterior hypothalamus. The thermostatic set point is then raised and mechanisms to conserve heat (vasoconstriction) and to produce heat (shivering) are initiated. The result is a sudden rise in body temperature. The same basic mechanisms are involved in FUO. Many of the biologic and biochemical changes that are seen in FUO are also evidence of an acute-phase response. The elevated erythrocyte sedimentation rate is partly due to increased synthesis of hepatic proteins, including compliment components, ceruloplasmin, fibrinogen, and C-reactive protein. IL-1 acts directly on the bone marrow to increase absolute numbers and immaturity of circulating neutrophils. Anemia is produced by many mechanisms, including the reduction of circulating serum iron. Although fever production in the elderly maybe delayed or of less intensity, it is still a marker of significant disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fever of unknown origin in the elderly. 266 44

Chronic inflammatory diseases are often associated with decreased red blood cell (RBC) mass. The cytokines cachectin/tumor necrosis factor-alpha (TNF) and interleukin 1 (IL 1) are produced by monocytes/macrophages in response to many inflammatory stimuli and have been implicated in the anemia of chronic disease. This study was undertaken to evaluate the mechanisms by which cachectin/TNF, IL 1, or endotoxin induce anemia. Hematologic parameters and RBC kinetics were quantitated in rats given chronic sublethal quantities of either recombinant human cachectin/TNF, recombinant human IL 1 alpha, or Salmonella endotoxin for 7 days. Cachectin/TNF or endotoxin treatment resulted in a 25 or 31% decrease, respectively, in total RBC mass, whereas RBC mass was unchanged by IL 1 administration. Anemia associated with either chronic cachectin or endotoxin administration was characterized by normal mean corpuscular volume, mean corpuscular hemoglobin content, and reticulocyte numbers. [59Fe]RBC survival was significantly shortened in animals given cachectin, IL 1 or endotoxin, but the magnitude of the response was greatest in cachectin/TNF-or endotoxin-treated rats. Although cachectin/TNF-IL 1-, or endotoxin treatment resulted in similar hypoferremia and shortened plasma iron half-life, endotoxin or cachectin/TNF treatment (but not IL 1) significantly reduced the incorporation of plasma 59Fe into newly synthesized RBCs. We conclude that chronic cachectin/TNF administration produces anemia by decreasing RBC synthesis and reducing the life span of circulating RBCs. An endogenous cachectin/TNF response during inflammatory disease may contribute to an associated anemic state, whereas the modestly reduced red cell life span induced by IL 1 does not lead to a net reduction in RBC mass, presumably owing to a preserved RBC synthetic rate.
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PMID:Cachectin/tumor necrosis factor-alpha alters red blood cell kinetics and induces anemia in vivo. 278 16


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